Early postnatal inhibition of GLAST causes abnormalities of psychobehaviors and neuronal morphology in adult mice.

The importance of glutamate transporters in learning, memory, and emotion remains poorly understood; hence, in the present study, we investigated whether deficiency of pharmacological GLAST in neurodevelopmental processes affects cognitive and/or emotional behaviors in mice. The mice were injected with a glutamate transporter inhibitor, dl-threo-ß-benzyloxyaspartate (dl-TBOA), during the early postnatal period. At 8 weeks of age, they showed impairments in cognitive or emotional behaviors; dysfunction of glutamatergic neurotransmission (increased expressions of GLAST, GLT-1, or GFAP protein, and decreased ability of glutamate release) in the cortex or hippocampus; morphological changes (decreased cell size in the cortex and thickness of the pyramidal neuronal layer of the CA1 area in the hippocampus). Such behavioral and morphological changes were not observed in adult mice injected with dl-TBOA. These results suggest that GLAST plays an important role in the regulation of cognitive and emotional behaviors. Early postnatal glutamatergic facilitation by GLAST dysfunction leads to cognitive and emotional abnormalities due to neurodevelopmental abnormalities such as morphological changes.

Dietary glutamic acid and aspartic acid as biomarkers for predicting diabetic retinopathy.

The screening rate of diabetic retinopathy (DR) is low despite the importance of early diagnosis. We investigated the predictive value of dietary glutamic acid and aspartic acid for diagnosis of DR using the Korea National Diabetes Program cohort study. The 2067 patients with type 2 diabetes without DR were included. The baseline intakes of energy, glutamic acid and aspartic acid were assessed using a 3-day food records. The risk of DR incidence based on intake of glutamic acid and aspartic acid was analyzed. The DR group was older, and had higher HbA1c, longer DM duration, lower education level and income than non-DR group (all p < 0.05). The intake of total energy, glutamic acid and aspartic acid were lower in DR group than non-DR group (p = 0.010, p = 0.025 and p = 0.042, respectively). There was no difference in the risk of developing DR according to the intake of glutamic acid and ascorbic acid. But, aspartic acid intake had a negative correlation with PDR. Hence, the intake of glutamic acid and aspartic acid did not affect in DR incidence. However, lower aspartic acid intake affected the PDR incidence.

Evaluation of anti-biofilm activity of acidic amino acids and synergy with ciprofloxacin on Staphylococcus aureus biofilms.

Acidic amino acids, aspartic acid (Asp) and glutamic acid (Glu) can enhance the solubility of many poorly soluble drugs including ciprofloxacin (Cip). One of the mechanisms of resistance within a biofilm is retardation of drug diffusion due to poor penetration across the matrix. To overcome this challenge, this work set to investigate novel counter ion approach with acidic amino acids, which we hypothesised will disrupt the biofilm matrix as well as simultaneously improve drug effectiveness. The anti-biofilm activity of D-Asp and D-Glu was studied on Staphylococcus aureus biofilms. Synergistic effect of combining D-amino acids with Cip was also investigated as a strategy to overcome anti-microbial resistance in these biofilms. Interestingly at equimolar combinations, D-Asp and D-Glu were able to significantly disperse (at 20 mM and 40 mM) established biofilms and inhibit (at 10 mM, 20 mM and 40 mM) new biofilm formation in the absence of an antibiotic. Moreover, our study confirmed L-amino acids also exhibit anti-biofilm activity. The synergistic effect of acidic amino acids with Cip was observed at lower concentration ranges (<40 mM amino acids and <90.54 µM, respectively), which resulted in 96.89% (inhibition) and 97.60% (dispersal) reduction in CFU with exposure to 40 mM amino acids. Confocal imaging indicated that the amino acids disrupt the honeycomb-like extracellular DNA (eDNA) meshwork whilst also preventing its formation.

Import of Aspartate and Malate by DcuABC Drives H2/Fumarate Respiration to Promote Initial Salmonella Gut-Lumen Colonization in Mice.

Initial enteropathogen growth in the microbiota-colonized gut is poorly understood. Salmonella Typhimurium is metabolically adaptable and can harvest energy by anaerobic respiration using microbiota-derived hydrogen (H2) as an electron donor and fumarate as an electron acceptor. As fumarate is scarce in the gut, the source of this electron acceptor is unclear. Here, transposon sequencing analysis along the colonization trajectory of S. Typhimurium implicates the C4-dicarboxylate antiporter DcuABC in early murine gut colonization. In competitive colonization assays, DcuABC and enzymes that convert the C4-dicarboxylates aspartate and malate into fumarate (AspA, FumABC), are required for fumarate/H2-dependent initial growth. Thus, S. Typhimurium obtains fumarate by DcuABC-mediated import and conversion of L-malate and L-aspartate. Fumarate reduction yields succinate, which is exported by DcuABC in exchange for L-aspartate and L-malate. This cycle allows S. Typhimurium to harvest energy by H2/fumarate respiration in the microbiota-colonized gut. This strategy may also be relevant for commensal E. coli diminishing the S. Typhimurium infection.

Aspartic acid supplementation ameliorates symptoms of diabetic kidney disease in mice.

Diabetic kidney disease (DKD) is among the most common and serious complications of both type 1 and type 2 diabetes. In this study, we used KK/Ta-Ins2Akita (KK-Akita) mice as a model of DKD and KK/Ta (KK) mice as controls to identify novel factors related to the development/progression of DKD. Capillary electrophoresis coupled with mass spectrometry analysis revealed that circulating Asp (l-aspartic acid) levels in diabetic KK-Akita mice tend to be lower than those in control KK mice. Therefore, we evaluated the effect of Asp supplementation to prevent the progression of DKD in KK-Akita mice. Mice were divided into three groups: (a) untreated KK mice (Control group), (b) untreated KK-Akita mice (DKD group), and (c) treated (double-volume Asp diet) KK-Akita mice (Tx group). Kidney sections were stained with fluorescein isothiocyanate-labeled lectins, wheat germ agglutinin (WGA), and anti-endothelial nitric oxide synthase (eNOS) antibody for evaluation of endothelial surface layer (ESL) and NO synthesis. The mesangial area and glomerular size in the DKD group were significantly larger than those in the Control group; however, there was no significant difference in those between the DKD and Tx groups. Albuminuria, the ratio of foot process effacement, and thickness of glomerular basement membrane in the Tx group were significantly lower than those in the DKD group. Furthermore, the expression levels of glomerular WGA and microvascular eNOS in the Tx group improved significantly and approached the level in the Control group. In conclusion, the improvement of albuminuria in the Tx group may be caused by the reduction of oxidative stress in the kidneys, which may lead to the subsequent improvement of glomerular ESL.

Aspartate racemase and D-aspartate in starfish; possible involvement in testicular maturation.

D-Aspartate, aspartate racemase activity, and D-aspartate oxidase activity were detected in tissues from several types of starfish. Aspartate racemase activity in male testes of Patiria pectinifera was significantly elevated in the summer months of the breeding season compared with spring months. We also compared aspartate racemase activity with the gonad index and found that activity in individuals with a gonad index ≥6% was four-fold higher than that of individuals with a gonad index <6%. The ratio of the D-form of aspartate to total aspartate was approximately 25% in testes with a gonad index <6% and this increased to approximately 40% in testes with a gonad index ≥6%. However, such changes were not observed in female ovaries. Administration of D-aspartate into male starfish caused testicular growth. These results indicate the possible involvement of aspartate racemase and D-aspartate in testicular maturation in echinoderm starfish.

l-aspartic acid promotes fish survival against Vibrio alginolyticus infection through nitric oxide-induced phagocytosis.

Bacterial infection severely impairs aquaculture development throughout the world. Despite the use of antibiotics to control bacterial infection, few other options are available especially in the area of complex ecosystem and various types of fish. In search for novel approaches in controlling bacterial infection, we adopt zebrafish, Danio reiro, as infection host and the bacteria, Vibrio alginolyticus, as pathogen to explore potential metabolites that boost host's capability to eliminate bacterial infection. By comparing the metabolome of dying fish, l-aspartic acid is a metabolite of differential abundance between the dying fish and surviving fish upon Vibrio alginolyticus infection. Exogenous l-aspartic acid increases fish survival rate from 46.67% to 76.67%. We further demonstrated that l-aspartic acid drives the production of nitrogen oxide that promotes phagocytosis. Whereas the inhibition of nitrogen oxide synthase would abolish l-aspartic acid-triggered phagocytosis as well as in vivo protective ability to V. alginolyticus. The importance of nitrogen oxide production in fish survival is also consistent with the observation in the dying fish that showed increased urea production but not nitrogen oxide. Thus, our results exemplify a novel approach in promoting fish survival in an eco-friendly way.

Effect of glutamate and aspartate on ischemic heart disease, blood pressure, and diabetes: a Mendelian randomization study.

BACKGROUND: Evolutionary biology suggests reproduction trades off against longevity. Genetic selection in favor of fertility and ischemic heart disease (IHD) exists in humans. Observationally, soy protects against IHD. Soy amino acids, glutamate and aspartate, may lower androgens. No large randomized controlled trials testing their health effects exist. OBJECTIVE: Using Mendelian randomization, we assessed how genetically predicted glutamate and aspartate affected IHD, blood pressure, and diabetes. METHODS: A separate sample instrumental variable analysis with genetic instruments was used to obtain unconfounded estimates using genetic variants strongly (P < 5 × 10(-8)) and solely associated with glutamate or aspartate applied to an IHD case (n ≤76,014)-control (n ≤ 264,785) study (based on a meta-analysis of CARDIoGRAMplusC4D 1000 Genomes, UK Biobank CAD SOFT GWAS and Myocardial Infarction Genetics and CARDIoGRAM Exome), blood pressure from the UK Biobank (n ≤ 361,194), and the DIAbetes Genetics Replication And Meta-analysis diabetes case (n = 26,676)-control (n = 132,532) study. A weighted median and MR-Egger were used for a sensitivity analysis. RESULTS: Glutamate was not associated with IHD, blood pressure, or diabetes after correction for multiple comparisons. Aspartate was inversely associated with IHD (odds ratio (OR) 0.92 per log-transformed standard deviation (SD); 95% confidence interval (CI) 0.88, 0.96) and diastolic blood pressure (-0.03; 95% CI -0.04, -0.02) using inverse variance weighting, but not diabetes (OR 1.00; 95% CI 0.91, 1.09). Associations were robust to the sensitivity analysis. CONCLUSIONS: Our findings suggest aspartate may play a role in IHD and blood pressure, potentially underlying cardiovascular benefits of soy. Clarifying the mechanisms would be valuable for IHD prevention and for defining a healthy diet.

Aspartic acid tagged carbon nanotubols as a tool to deliver docetaxel to breast cancer cells: Reduced hemotoxicity with improved cytotoxicity.

The present study aimed to explore the potential of hydroxylated carbon nanotubes (CNTnols) conjugated with aspartic acid for the delivery of docetaxel (DTX) to breast cancer cells. The conjugate was well-characterized by FT-IR, NMR, XRD and FE-SEM. The nanoconjugate offered a hydrodynamic diameter of 86.31 ±â€¯1.02 nm, with a PDI of 0.113 and zeta potential of -41.6 ±â€¯0.17 mV. The designed nanosystem offered a controlled & pH dependent release vouching release of drug in the cancerous cytosol, not in blood, assuring delivery of the pay-load to the site of action. The carriers offered substantial hemocompatibility and lower plasma protein binding, ensuring more drug available at the site of action. The in-vitro cell viability studies in MDA MB-231 cells inferred approx. 2.8 times enhancement in the cytotoxicity potential of the conjugate vis-à-vis plain drug. Pharmacokinetic studies also corroborated the superiority of the designed nanoconjugate in terms of enhanced bioavailable fractions, reduced clearance and longer bioresidence to that of plain docetaxel. The present studies, successfully provide a workable nanomedicine, loaded with a BCS class-IV drug, for improved efficacy and safety in breast cancer.

One-trial learning in larval Drosophila.

Animals of many species are capable of "small data" learning, that is, of learning without repetition. Here we introduce larval Drosophila melanogaster as a relatively simple study case for such one-trial learning. Using odor-food associative conditioning, we first show that a sugar that is both sweet and nutritious (fructose) and sugars that are only sweet (arabinose) or only nutritious (sorbitol) all support appetitive one-trial learning. The same is the case for the optogenetic activation of a subset of dopaminergic neurons innervating the mushroom body, the memory center of the insects. In contrast, no one-trial learning is observed for an amino acid reward (aspartic acid). As regards the aversive domain, one-trial learning is demonstrated for high-concentration sodium chloride, but is not observed for a bitter tastant (quinine). Second, we provide follow-up, parametric analyses of odor-fructose learning. Specifically, we ascertain its dependency on the number and duration of training trials, the requirements for the behavioral expression of one-trial odor-fructose memory, its temporal stability, and the feasibility of one-trial differential conditioning. Our results set the stage for a neurogenetic analysis of one-trial learning and define the requirements for modeling mnemonic processes in the larva.

A Phase 2 Study of PCI-27483, a Factor VIIa Inhibitor in Combination with Gemcitabine for Advanced Pancreatic Cancer.

OBJECTIVES: Tissue factor overexpression is associated with tumor progression, venous thromboembolism, and worsened survival in patients with cancer. Tissue factor and activated factor VII (FVIIa) complex may contribute to tumor invasiveness by promoting cell migration and angiogenesis. The study objective was to evaluate safety, pharmacokinetics, and efficacy of PCI-27483, a selective FVIIa inhibitor. METHODS: This was an open-label, multicenter phase 2 trial of patients with advanced pancreatic cancer. Part A of the study was an intrapatient dose escalation lead-in portion in patients concurrently receiving gemcitabine, and in part B, patients were randomized 1: 1 to the recommended phase 2 dose combination PCI-27483-gemcitabine versus gemcitabine alone. RESULTS: Target international normalized ratio (between 2.0-3.0) was achieved following PCI-27483 treatment. Overall safety of PCI-27483-gemcitabine (n = 26) was similar to gemcitabine alone (n = 16), with a higher incidence of mostly low-grade bleeding events (65% vs. 19%). Progression-free survival (PFS) and overall survival (OS) were not significantly different between patients treated with PCI-27483-gemcitabine (PFS: 3.7 months, OS: 5.7 months) and those treated with gemcitabine alone (PFS: 1.9 months, OS: 5.6 months). CONCLUSIONS: Targeted inhibition of the coagulation cascade was achieved by administering PCI-27483. PCI-27483-gemcitabine was well tolerated, but superiority to single agent gemcitabine was not demonstrated.

d- and l-Aspartate regulates growth performance, inflammation and intestinal microbial community in young pigs.

d-aspartate (d-Asp), an endogenous amino acid, occurs widely in animals and humans with d-enantiomers and plays an important role in the endocrine and nervous systems. However, very few studies are available on growth performance, microbial community, and the intestinal immune and inflammatory status in response to d- and l-aspartate (l-Asp). Thus, in this study, we mainly investigated the effects of dietary 1% d- and l-Asp on growth performance, inflammation, and microbial community in young pigs. Twenty-eight young pigs were randomly divided into four groups (n = 7): a control group, in which piglets were fed a basal diet, and other three groups, in which piglets received 1% d-Asp, 1% l-Asp, and 1% dl-aspartate (dl-Asp) for 35 days. The results showed that dietary 1% d-Asp significantly inhibited average daily feed intake and average daily weight gain. Gut microbes were tested and the results showed that l-Asp enhanced bacterial diversity (Shannon and Simpson). At the phylum level, l-Asp enhanced intestinal Actinobacteria and Bacteroidetes abundance but decreased Firmicutes abundance. In contrast, dl-Asp decreased intestinal Actinobacteria and Bacteroidetes abundance and increased Firmicutes abundance. At the genus level, d-Asp enhanced Clostridium sensu stricto 1 and Intestinibacter abundance. Metagenomic predictions by PICRUSt suggested that the altered microbiota were mainly involved in membrane transport, carbohydrate metabolism, amino acid metabolism, replication and repair, translation, and nucleotide metabolism. In addition, dl-Asp markedly increased the activities of serum alanine aminotransferase, aspartate transaminase and alkaline phosphatase. Also, dietary d- and dl-Asp down-regulated TLR 4, NOD1, and MyD88 in the jejunum to mediate the inflammatory response. Collectively, these results indicated that dietary d-Asp and l-Asp affect the growth performance and inflammation in piglets, which might be associated with gut microbiota.

Bone-Fracture-Targeted Dasatinib-Oligoaspartic Acid Conjugate Potently Accelerates Fracture Repair.

Approximately 6.3 million bone fractures occur annually in the United States, resulting in considerable morbidity, deterioration in quality of life, loss of productivity and wages, and sometimes death (e.g., hip fractures). Although anabolic and antiresorptive agents have been introduced for treatment of osteoporosis, no systemically administered drug has been developed to accelerate the fracture-healing process. To address this need, we have undertaken to target a bone anabolic agent selectively to fracture surfaces in order to concentrate the drug's healing power directly on the fracture site. We report here that conjugation of dasatinib to a bone fracture-homing oligopeptide via a releasable linker reduces fractured femur healing times in mice by ∼60% without causing overt off-target toxicity or remodeling of nontraumatized bones. Thus, achievement of healthy bone density, normal bone volume, and healthy bone mechanical properties at the fracture site is realized after only 3-4 weeks in dasatinib-targeted mice, but it requires ∼8 weeks in PBS-treated controls. We conclude that targeting of dasatinib to bone fracture surfaces can significantly accelerate the healing process at dasatinib concentrations that are known to be safe in oncological applications.

A delta opioid receptor agonist, KNT-127, in the prelimbic medial prefrontal cortex attenuates glial glutamate transporter blocker-induced anxiety-like behavior in mice.

We previously reported that systemic administration of a delta opioid receptor (DOP) agonist, KNT-127, produced a potent anxiolytic-like effect in rats. Interestingly, DOPs are highly distributed in the prelimbic medial prefrontal cortex (PL-PFC). In the present study, we investigated the effect of KNT-127 co-perfusion in the PL-PFC on anxiety-like behavior in mice, induced by a glial glutamate transporter inhibitor, (3S)-3-[[3-[[4-(Trifluoromethyl)benzoyl]amino]phenyl]methoxy]-l-aspartic acid (TFB-TBOA). Extracellular glutamate levels were measured in male C57BL/6N mice by in vivo microdialysis high-performance liquid chromatography/electrochemical detection, with behavior simultaneously assessed in the open field test. As expected, extracellular glutamate levels were significantly increased, and anxiety-like behavior was induced after local perfusion of TFB-TBOA in the PL-PFC. Uniquely, co-perfusion of KNT-127 in the PL-PFC diminished anxiety-like behavior induced by TFB-TBOA without affecting extracellular glutamate levels. Further, the effect of KNT-127 on anxiety-like behavior was antagonized by a selective DOP antagonist, naltrindole, suggesting that KNT-127 acts via DOPs. These findings do not support our preconceived hypothesis that KNT-127 in PL-PFC produces an anxiolytic-like effect via suppression of glutamatergic transmission. Hence, further studies are necessary to understand the mechanisms of DOP agonist-induced anxiolytic-like effects in the PL-PFC.

Effects of Magnesium Supplementation on Unipolar Depression: A Placebo-Controlled Study and Review of the Importance of Dosing and Magnesium Status in the Therapeutic Response.

Animal studies using tests and models have demonstrated that magnesium exerts an antidepressant effect. The literature contains few studies in humans involving attempts to augment antidepressant therapy with magnesium ions. The purpose of our study was to assess the efficacy and safety of antidepressant treatment, in combination with magnesium ions. A total of 37 participants with recurrent depressive disorder who developed a depressive episode were included in this study. As part of this double-blind study, treatment with the antidepressant fluoxetine was accompanied with either magnesium ions (120 mg/day as magnesium aspartate) or placebo. During an 8-week treatment period, each patient was monitored for any clinical abnormalities. Moreover, serum fluoxetine and magnesium levels were measured, and pharmaco-electroencephalography was performed. The fluoxetine + magnesium and fluoxetine + placebo groups showed no significant differences in either Hamilton Depression Rating Scale (HDRS) scores or serum magnesium levels at any stage of treatment. Multivariate statistical analysis of the whole investigated group showed that the following parameters increased the odds of effective treatment: lower baseline HDRS scores, female gender, smoking, and treatment augmentation with magnesium. The parameters that increased the odds of remission were lower baseline HDRS scores, shorter history of disease, the presence of antidepressant-induced changes in the pharmaco-EEG profile at 6 h after treatment, and the fact of receiving treatment augmented with magnesium ions. The limitation of this study is a small sample size.

Noninvasive Tracking of Anesthesia Neurotoxicity in the Developing Rodent Brain.

BACKGROUND: Potential deleterious effect of multiple anesthesia exposures on the developing brain remains a clinical concern. We hypothesized that multiple neonatal anesthesia exposures are more detrimental to brain maturation than an equivalent single exposure, with more pronounced long-term behavioral consequences. We designed a translational approach using proton magnetic resonance spectroscopy in rodents, noninvasively tracking the neuronal marker N-acetyl-aspartate, in addition to tracking behavioral outcomes. METHODS: Trajectories of N-acetyl-aspartate in anesthesia naïve rats (n = 62, postnatal day 5 to 35) were determined using proton magnetic resonance spectroscopy, creating an "N-acetyl-aspartate growth chart." This chart was used to compare the effects of a single 6-h sevoflurane exposure (postnatal day 7) to three 2-h exposures (postnatal days 5, 7, 10). Long-term effects on behavior were separately examined utilizing novel object recognition, open field testing, and Barnes maze tasks. RESULTS: Utilizing the N-acetyl-aspartate growth chart, deviations from the normal trajectory were documented in both single and multiple exposure groups, with z-scores (mean ± SD) of -0.80 ± 0.58 (P = 0.003) and -1.87 ± 0.58 (P = 0.002), respectively. Behavioral testing revealed that, in comparison with unexposed and single-exposed, multiple-exposed animals spent the least time with the novel object in novel object recognition (F(2,44) = 4.65, P = 0.015), traveled the least distance in open field testing (F(2,57) = 4.44, P = 0.016), but exhibited no learning deficits in the Barnes maze. CONCLUSIONS: Our data demonstrate the feasibility of using the biomarker N-acetyl-aspartate, measured noninvasively using proton magnetic resonance spectroscopy, for longitudinally monitoring anesthesia-induced neurotoxicity. These results also indicate that the neonatal rodent brain is more vulnerable to multiple anesthesia exposures than to a single exposure of the same cumulative duration.

Effects of three major amino acids found in Japanese broth on glucose metabolism and gastric emptying.

OBJECTIVES: To our knowledge, the effect of the broth of dried kelp and dried bonito, dashi, on glucose metabolism and digestion has rarely been studied. Based on the component analysis of three actual broths served in traditional restaurants, a chemically synthesized broth with three free amino acids (histidine, glutamate, aspartate) and salt was prepared to investigate their effect on glucose metabolism, glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide 1 (GLP-1) secretion, and digestion. METHODS: In study 1, seven healthy individuals were enrolled in a four-period crossover study. Participants drank or ate hot water, synthesized broth, hot water with rice, and synthesized broth with rice. Plasma glucose, serum insulin, plasma glucagon, plasma GIP, and plasma GLP-1 were measured at baseline and after ingestion. In study 2, 6 of the 7 individuals ingested rice steamed with 13C-labeled sodium acetate with hot water or synthesized broth to estimate gastric emptying by the 13C-labeled acetate breath test in a two-period crossover trial. RESULTS: Ingesting water or synthesized broth alone elicited no change in plasma glucose or serum insulin levels. Ingesting synthesized broth with rice resulted in a rapid rise in plasma glucose and GLP-1 (P = 0.01 and 0.02, respectively) in an early postprandial phase compared with that by ingesting water with rice, but the area under the curve of those showed no significant differences. Ingesting synthesized broth with rice resulted in a significantly higher gastric emptying coefficient than that after rice with water (P = 0.03). CONCLUSIONS: Three amino acids and sodium chloride corresponding to those found in actual broth promoted gastric emptying and led to a rapid response of plasma glucose. Our findings suggest that ingestion of the broth of dried kelp and dried bonito may improve gastric motility.

Foliar application of aspartic acid lowers cadmium uptake and Cd-induced oxidative stress in rice under Cd stress.

Cadmium (Cd) contamination of farmland soils is a widespread problem around the globe, and rice (Oryza sativa L.) tends to accumulate more Cd and is considered as one of the major sources of Cd intake in humans, especially consuming rice-derived products. The current study investigated the effects of foliar applied aspartic acid (Asp) on growth parameters, biomass, chlorophyll concentration, gas exchange characteristics, Cd uptake, and antioxidative capacity in the shoots and roots of rice seedlings exposed to Cd stress. For this, 30-day-old rice nursery was transferred in the soil with aged Cd contamination (2.86 mg kg-1). After 2 weeks of growth, different concentrations (0, 10, 15, and 20 mg L-1) of Asp were foliar applied four times with a 7-day interval, and the crop was harvested after 10 weeks of transplanting. Foliar applied Asp increased the plant height, shoot and root dry weight, chlorophyll concentration, and gas exchange parameters, while it reduced the Cd concentrations in both shoots and roots as well as shoot to root Cd translocation factor compared to the control. Foliar application of Asp reduced the malondialdehyde content and electrolyte leakage in rice parts compared to the control in a dose-additive manner. The activities of key antioxidant enzymes increased while peroxidase activity decreased by exogenous Asp. The increase in plant weight and photosynthesis might be due to lower Cd concentrations in plants which may reduce the oxidative stress and also help the plants to minimize direct damage caused by Cd to the photosynthetic organs.

The effect of aspartate supplementation on the microbial composition and innate immunity on mice.

The study was conducted to investigate the changes of intestinal microbiota composition and innate immunity with different dietary dosages of aspartate (Asp) supplementation. Thirty-six female ICR mice were divided randomly to four groups and thereafter fed the basal diets (controls) or those supplemented with additional 0.5, 1.0 and 2.0% aspartate. After 2 week feeding, microbial composition in ileum and feces, gene expression of pro-inflammatory cytokine, and innate immune factors in ileum were determined. The ratio of Firmicutes: Bacteroidetes in ileum and feces decreased in 0.5 and 1.0% Asp-supplemented groups, whereas this ratio increased in feces in 2.0% Asp-supplemented group. Meanwhile, the gene expression of IL-17 and IFN-γ in ileum decreased in 1.0% Asp-supplemented group; the gene expression in ileum of Muc2 decreased in 0.5 and 1.0% Asp-supplemented groups. Dietary supplementation with 2.0% Asp enhanced the expression of pIgR and Crp1 as compared to the other three groups. The results indicated that dietary 1.0% Asp supplementation lowers the ratio of Firmicutes:Bacteroidetes, which affects the innate immunity by decreasing the gene expression of IL-17, IFN-γ, and Muc2 in ileum.

Nutritional control of antibiotic production by Streptomyces platensis MA7327: importance of l-aspartic acid.

Streptomyces platensis MA7327 is a bacterium producing interesting antibiotics, which act by the novel mechanism of inhibiting fatty acid biosynthesis. The antibiotics produced by this actinomycete are platensimycin and platencin plus some minor related antibiotics. Platensimycin and platencin have activity against antibiotic-resistant bacteria such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus; they also lack toxicity in animal models. Platensimycin also has activity against diabetes in a mouse model. We have been interested in studying the effects of primary metabolites on production of these antibiotics in our chemically defined production medium. In the present work, we tested 32 primary metabolites for their effect. They included 20 amino acids, 7 vitamins and 5 nucleic acid derivatives. Of these, only l-aspartic acid showed stimulation of antibiotic production. We conclude that the stimulatory effect of aspartic acid is due to its role as a precursor involved in the biosynthesis of aspartate-4-semialdehyde, which is the starting point for the biosynthesis of the 3-amino-2,4-dihydroxy benzoic acid portion of the platensimycin molecule.